Document Detail


Target selection of heparan sulfate hexuronic acid 2-O-sulfotransferase.
MedLine Citation:
PMID:  20554947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The signaling of various molecules involved in development and regulation of cell growth are regulated by heparan sulfate (HS). Specific binding of HS to ligand proteins depends on the HS sulfation pattern, where the spacing and number of O-sulfate groups are of special importance. HS 2-O-sulfotransferase catalyzes 2-O-sulfation of glucuronic and iduronic acid residues with a 5-fold higher preference for iduronic acid, as inferred from previously determined kinetic parameters. To study in more detail the regulation of HS hexuronic acid 2-O-sulfation, we tested the ability of the enzyme to catalyze glucuronic acid 2-O-sulfation in polysaccharide mixtures with different glucuronic acid/iduronic acid ratios, using 3'-phosphoadenosine 5'-phospho[(35)S]sulfate as sulfate donor. The 2-O-sulfotransferase revealed a more pronounced preference for 2-O-sulfation of iduronic acid than predicted. Even incubations with a 99:1 ratio of glucuronic acid to iduronic acid resulted in almost exclusive iduronic acid 2-O-sulfation. Unexpectedly, when the 2-O-sulfotransferase was co-immunoprecipitated with the glucuronyl C5-epimerase (that converts glucuronic acid to iduronic acid), both glucuronic acid and iduronic acid residues were sulfated to the same extent when a polysaccharide containing only glucuronic acid was used as a substrate. Attempting to understand the mechanism by which extended regions of iduronic acid 2-O-sulfation are formed during HS biosynthesis, a (3)H-labeled N-sulfated iduronic acid containing octasaccharide substrate was incubated with the 2-O-sulfotransferase and 3'-phosphoadenosine 5'-phosphosulfate. The 2-O-sulfotransferase showed a preference for mono-2-O-sulfated substrates as compared with octasaccharides with no 2-O-sulfate group.
Authors:
Emanuel Smeds; Almir Feta; Marion Kusche-Gullberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-16
Journal Detail:
Title:  Glycobiology     Volume:  20     ISSN:  1460-2423     ISO Abbreviation:  Glycobiology     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-09-08     Completed Date:  2011-01-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1274-82     Citation Subset:  IM    
Affiliation:
Department of Biomedicine, University of Bergen, Jonas Lies vei 91, Bergen, Norway.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blotting, Western
Cells, Cultured
Glucuronic Acid / metabolism*
Heparitin Sulfate / metabolism*
Humans
Iduronic Acid / metabolism*
Kidney / cytology,  metabolism
Mice
Polysaccharides / metabolism*
Substrate Specificity
Sulfotransferases / metabolism*
Chemical
Reg. No./Substance:
0/Polysaccharides; 3402-98-0/Iduronic Acid; 576-37-4/Glucuronic Acid; 9050-30-0/Heparitin Sulfate; EC 2.8.2.-/Sulfotransferases; EC 2.8.2.-/heparan-sulfate 2-sulfotransferase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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